The determination of blood glucose is critical to diabetic patients. These patients must measure their blood glucose level several times daily in order to determine how much insulin their body requires. For diabetics with internally implantable or external insulin pumps, the ability to have a reliable glucose sensor that can continuously measure their blood glucose is essential for the realization of an artificial pancreas device.
Considerable efforts have been placed on the development of reliable methods for measuring blood glucose noninvasively. Although several sensors have been successfully developed for in vitro and in vivo applications, these sensors can be used only for intermittent measurements or short term monitoring. None of these devices are suitable for long-term in vivo applications utilizing noninvasive means.
The concentration of a limited number of analytes in blood can be measured noninvasively by spectroscopic means. For instance, by measuring the amount of optical radiation either absorbed by, transmitted through or reflected from biological tissues, it is possible to derive a quantitative measurement relative to the concentration of oxygen in blood. In contrast to invasive measurement, noninvasive measurements are clearly more attractive because they are safe, fast, convenient, painless and can be used to provide short-term and long-term continuous information on changing levels of blood analytes in the body. Therefore, noninvasive measurement of blood constituents is desirable, especially in children and older patients.
Several attempts have been made in the past to develop a reliable method for quantitative noninvasive measurement of glucose levels in biological tissues by irradiating the tissue with light at predetermined wavelengths and using the principle of absorption spectroscopy. Some methods are based on detecting the resonance absorption peaks in the infrared region of the electromagnetic spectrum, also known as the "fingerprints" region, which are caused by vibrational and rotational oscillations of the molecules and are characteristic for different molecules. Other techniques are based upon near-infrared spectroscopy to determine the sample's composition. Unlike the "fingerprint" region, which is valuable as a tool for obtaining structural information on the sample, structural measurements in the near infrared region of the spectra are obscured because of multiple and weak overtones yielding many overlapping peaks.
Regardless of which spectroscopic method is employed, there are four basic practical difficulties which limit the noninvasive detection of most biological substances including glucose: 1) The high intrinsic background absorption by water, 2) the relatively low concentration of most biological substances, 3) the number of weak and overlapping absorption peaks in the spectra, and 4) the highly scattering properties of biological tissues. Moreover, the large variations in the optical properties of skin among different individuals makes absolute measurements and calibrations very difficult and impractical.
Two methods are commonly utilized for obtaining spectral information from biological tissues for the purpose of measuring the concentration of various biochemical constituents noninvasively. One method is based on information derived from the absolute optical spectra of tissues containing blood. According to this concept, the tissue is illuminated with light at different preselected wavelengths and either the total or proportional amount of light which is transmitted through, reflected from, or transflected by the tissue is measured by a photodetector. This technique was utilized for example by Hewlett-Packard in their ear oximeter product (U.S. Pat. No. 3,638,640 by Shaw) and by Rosenthal et al. (U.S. Pat. No. 5,028,787). According to the other method, which is widely used in pulse oximetry, the tissue is illuminated by two different light sources. Typically, one wavelength around 660 nm and the other in the range between 815 nm and 960 nm are used. The change in optical absorption caused by the pulsation of arterial blood in the tissue is measured and analyzed to provide a quantitative measure of the amount of oxygen present in the arterial blood. According to this second technique, the ratio between the normalized pulsatile and nonpulsatile components of a single pair of red and infrared wavelengths transmitted through tissue is used to compute the amount of oxygen saturation in the arterial blood. Both of these methods are useful for measuring, for example, the oxygen saturation in blood but cannot be readily utilized for measuring the concentration of glucose or other low concentration substances in blood. The reasons are related to the fact that the optical absorption spectra of oxyhemoglobin, which corresponds to fully oxygenated blood, and deoxyhemoglobin, which corresponds to fully deoxygenated blood, are significantly different from each other. Furthermore, the optical absorption spectra of blood in the 660 to 9660 nm region of the spectrum is significantly stronger than the background optical absorption of the blood-less tissue. Lastly, the relative concentration of hemoglobin is normally about 150 times higher than that of glucose and hemoglobin has a much higher optical absorption compared to that of glucose.